The polypeptides of the invention have an amino acid sequence derived from one of the conserved consensus domains of SCO-spondin called thrombospondin type 1 repeat or TSR.
It is well known that different synthetic peptides deduced from the structure of thrombospondin have interesting effects on different cell types, in particular they inhibit tumors in mammals, influence thrombolysis and angiogenesis and may be complementary modulators or even ensure the promotion of cell attachment [Sipes J M et al., J Cell Biol, 121, 469-77, 1993; Rusnati M et al. Pharmaceuticals 3, 1241-1278, 2010; Lopez-Dee Z et al., Mediators of Inflammation, Volume 2011, Article ID 296069, 10 pages, 201i].
The general characteristics of SCO-spondin are described in particular in the article by Meiniel et al., Microsc Res Tech. 2, 484-95, 2001 and the article by Gobron et al. Glia 32, 177-91, 2000.
The application of an amino acid sequence polypeptide: W-S-G-W-S-S-C-S-R-S-C-G, [SEQ ID NO: 58] corresponding to the most representative amino acid sequence of one of the SCO-spondin TSR motifs, leads in the B104 cells from rat neuroblastoma a cell differentiation inducing neuritic growth and cell aggregation [F. El-Bitar et al., Cell Tissue Res., Vol. 304, p. 361-369.2001]. This polypeptide does not have a disulfide bridge between the two cysteines.
This polypeptide as well as the reduced form polypeptides of formula SEQ ID NO: 70 and, in particular, of formula SEQ ID NO: 57 are described and claimed in international patent applications WO 1999/03890 (corresponding to U.S. Pat. No. 6,995,140) and WO2009027350, or may be prepared based on the description of these patents and methods known to those skilled in the art.
However, the stability of the polypeptide W-S-G-W-S-S-C-S-R-S-C-G [SEQ ID NO: 58] decreases in aqueous solution over time. It would therefore be necessary for this polypeptide to be prepared extemporaneously during the treatments, which could complicate the administration thereof, thus limiting the possibilities of carrying out treatments by direct injection, or, for example, by means of pumps for the progressive delivery of the medicament to the patients. In general, this low stability would present a certain disadvantage for the development of therapeutic concepts based on this polypeptide.
Patent application WO 2008/090285 discloses peptido-mimetic analogs of the polypeptide W-S-G-W-S-S-C-S-R-S-C-G [SEQ ID NO: 58]. This approach, however, has two disadvantages: these polypeptides contain non-natural amino acids that are likely to cause immunogenicity phenomena, and a significant increase in production costs, while non-natural amino acids are much more expensive than natural amino acids, which diminishes their commercial interest.